Drug Interactions between mycophenolic acid and Premphase

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with mycophenolic acid may decrease the plasma concentrations and, theoretically, the efficacy of contraceptive hormones. The mechanism of interaction has not been established. In 18 women with psoriasis who were studied over 3 consecutive menstrual cycles, administration of combined oral contraceptives containing ethinyl estradiol (0.02 to 0.04 mg) and levonorgestrel (0.05 to 0.20 mg), desogestrel (0.15 mg), or gestodene (0.05 to 0.10 mg) during treatment with mycophenolate mofetil 1 gram twice daily resulted in a 15% reduction in mean levonorgestrel systemic exposure (AUC). No significant changes in mean AUC for ethinyl estradiol and 3-keto desogestrel were observed. However, there was a large interpatient variability in the data, especially for ethinyl estradiol. Mean serum levels of LH, FSH, and progesterone were not significantly affected in the study.

MANAGEMENT: Although clinical significance of the interaction is unknown, caution is advised when mycophenolic acid is prescribed in combination with hormonal contraceptives, including all oral, injectable, transdermal, vaginal, and implantable forms. Because use of mycophenolic acid is associated with an increased risk of pregnancy loss in the first trimester and congenital malformations, it is particularly important that female patients not become pregnant during treatment. An acceptable barrier method (e.g., diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male condom, female condom) should be used in addition to the hormonal contraceptive of choice during the entire duration of mycophenolic acid therapy and for 6 weeks after discontinuation. Input from a gynecologist or similar expert on adequate contraception should be sought as needed. Intrauterine systems are unlikely to be significantly affected because of their local action.